We have previously demonstrated that extracranial sensors (other than the carotid and aortic bodies) mediate the ventilatory response to drug-induced hypermetabolism. The present program will use regional perfusion techniques to anatomically localize these extracranial receptors. We have also demonstrated that intra-aortic cyanide infusions, which elicit metabolic changes of hypoxia, stimulate ventilation independent of conventional chemical stimuli in arterial blood or in cisternal cerebrospinal fluid (i.e. arterial oxygen saturation, arterial pCO2, arterial pH and cisternal CSF pH). Head-perfused animal experiments have demonstrated that extracranial sensors (other than the carotid and aortic bodies) mediate the hyperventilation elicited by intra-aortic cyanide infusion. The present program will discern the ventilatory response of these extracranial sensors to tissue metabolic changes of hypoxia elicited by arterial hypoxemia. We intend to perfuse the head and innervated arterial chemoreceptors with hyperoxemic blood while the remainder of the animal will be exposed to hypoxemic blood. This protocol will prevent hypoxemia-induced central ventilatory depression from obscuring possible ventilatory stimulation by extra- cranial tissue hypoxia. Bibliographic references: Levine, S., and W. E. Huckabee. Ventilatory response to drug-induced hypermetabolism. Journal of Applied Physiology 38:827-833, 1975; Levine, S. Ethyl Methylene blue and cyanide-induced lactic acidemia. Federation Proceedings 34:480, 1975.